2023 Fiscal Year Final Research Report
Development of radionuclide therapy with a fusion of CSC binding peptides and high energy alpha nuclides
| Project/Area Number |
21H02794
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Review Section |
Basic Section 50020:Tumor diagnostics and therapeutics-related
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| Research Institution | National Cancer Center Japan |
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Principal Investigator |
Mitsuyoshi Yoshimoto 国立研究開発法人国立がん研究センター, 先端医療開発センター, 主任研究員 (00345638)
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| Co-Investigator(Kenkyū-buntansha) |
和田 俊一 大阪医科薬科大学, 薬学部, 准教授 (30278593)
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| Project Period (FY) |
2021-04-01 – 2024-03-31
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| Keywords | アルファ線核種 / ペプチド / CD44 / がん幹細胞 / CD44 |
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| Outline of Final Research Achievements |
Based on compounds that have been reported as CD44-binding peptides, three types of peptides (DOTA-A5G27, DOTA-RP-1, DOTA-P7) conjugated with a chelating agent (DOTA) for labeling metal radionuclides such as 111In were synthesized. All peptides could be labeled with 111In in high yield. Furthermore, 225Ac labeling was also investigated, but it was confirmed that the labeling efficiency was poor. We investigated the pharmacokinetics of 111In-labeled peptides in BxPC-3 and U-87 MG bearing nude mice. Unfortunately, the tumor uptake of these peptides was extremely low. In in vitro competitive inhibition experiments, the tumor uptake of 111In-DOTA-RP-1 was inhibited by hyaluronic acid.
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| Free Research Field |
核医学治療
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| Academic Significance and Societal Importance of the Research Achievements |
CD44結合ペプチドとして報告されている化合物を参考に、核医学治療薬剤の開発を試みた。キレート剤を結合させることにより、放射性金属核種（111Inや225Ac）を標識することは可能であった。しかしながら、治療可能な照射線量を付与できる腫瘍集積を確認することはできなかった。投与後早期から肝臓への高集や速やかな体外排泄が、腫瘍集積を妨げる要因であると考えられた。これらの知見は、核医学治療用ペプチドの開発を進めるうえで、非常に意義あるものと考える。
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